What Is Epigenetics?

Is the study of heritable and potentially reversible gene-expression changes that do not involve structural alterations in the DNA sequence, such as mutations. ?Is emerging as one of the most dynamic and vibrant biomedical areas . EPIGENETICS MECHANISMS ?Epigenetics is the study of heritable and potentially reversible gene expression changes that do not involve structural alterations. ?DNA sequence,such as mutations. This term was coined to describe changes that could not be explained by genetic mechanisms .

These major types of epigenetic changes have been describe:DNA methylation, covalent post translational histone modification and small inhibitory RNA-mediated signaling pathways. ?DNA methylation is the most extensively studied epigenetic modification in humans. Epigenetic reprogramming during mammalian development ? In at least two developmental stags in mammals ,gametogenesis and pre-implantation development ,the DNA methylation pattern is reprogrammed genome-wide.

This epigenetic reprogramming is believed to be necessary for return to pluripotency and for lineage commitment. ?In mammals, the genomes of mature sperm cells and egg remain highly methylated until fertilization. During pre-implantation development, a second round of demethylation takes place in the zygote, occuring at different rates in the two parental genomes. ?Demethylation of the paternal genome- occurs after fertilization but before cell division, it is more rapid than in the maternal genome, and involves an active mechanism.

Demethylation of the maternal genome- occurs gradually over the first few cleavage divisions of the embryo, involves a passive mechanism, and is dependent on DNA replication ? Both the paternal and the maternal genomes are remethylated around the time of implantation. Epigenetics and cancer ?Cancer cells often show global DNA hypomethylation, a modification associated with chromosomal instability, hypermethylation at promoter CpG sites, which causes aberrant genes silencing, and disruption in the normal pattern of covalent histone modifications.

The global loss of histone H4K20 trimethylation and histone H4k16 acetylation are among the frequently described changes that occur in cancer cells. ?(2009) Kitago- revealed, for the first time, that the mRNA for RUNX3, a tumor suppressor gene involved in several cancers, is suppressed in primary cutaneous melanoma and is further suppressed in metastatic tumors, as compared with normal tissue. ?(2007) Nobeyama- reported hypermethylation of the TFP12 tumor suppressor gene in 29% of the metastatic melanomas examined, but in none of their primary tumors of origin.

These findings point toward the involvement of hypermethylation and gene inactivation in tumor metatesis. An epigenetic switch ?By transiently activating with tamoxifen a fusion construct between the (v-Src) and the ligand-binding domain of estrogen receptor, ? (2009) iliopoulus- revealed that the inflamatory response initiated an epigenetic switch and, as a result, a non-transformed state. ?The authors subsequently identified two microRNAs,miR-21 and miR-181-b1, which are known to be involved in human cancers, and are differentially regulated as part of this positive feedback loop.

The transient expression of either of these microRnas was sufficient to activate the epigenetic switch and cause transformation. Case studies: Epigenetics & Environmental Exposures ?For many years, it was erroneously assumed that, to cause cancer, a compound has to cause mutations in the double-stranded DNA, and mutation were viewed as the only way that could lead to carcinogenosis. Consequently it was assumed, equally erroneously , that a compound cannot cause cancer as long as it does not mutate the DNA.?

1. Arsenic- a human carcinogen causally linked to skin, liver, lung, and bladder cancer, does not appear to be mutagenic and does not induce point mutations in standard mutagenesis assays. ?2. Infectious Diseases- the human papilloma virus, hepatitis B virus, and certain helicobacter pylori strains are among the most extensively studied microorganism, causally linked, respectively, to cancer of the cervix and esophagus, liver and stomach.

> Fernandez (2009) reported for the first time a dynamic methylation pattern that occurs in several double-stranded cancer-causing DNA viruses. ?3. Polycyclic Aromatic Hydrocarbons & Chemicals from Cigarette Smoke- one of the most extensively studied environmental toxins is tobacco smoke, a mixture of >4000 chemicals, at least 62 of which show sufficient evidence of human or animal carcinogenicity. Certain components of cigarette smoke are mutagens, but increasing numbers of studies describe epigenetic perturbations as a result of exposure.

Polycyclic aromatic hydrocarbons (PAHs) are among of the most extensively studied chemicals from cigarette smoke. ?4. Social and Emotional Factors- social interactions were recently linked to epigenetic changes, possibly via hormonal pathways. Several recent findings reveal that epigenetic changes could help understand the biological basis of posttraumatic stress disorder. ?5. Dietary Factors- the intrauterine environment is instrumental for offspring development and perturbations during this stage may have long-lasting consequences in the adult.

The effects of maternal nutritional deprivation during pregnancy on the risk of adult-onset disease are illustrated by studies from the Dutch Hunger Winter, also known as the Dutch Famine. The “Barker hypothesis,” also known as the “developmental origins of health and disease,” is concept used to describe the increased risk of developing adult-onset chronic diseases by adults exposed to unfavorable conditions during intrauterine development.

REFERENCES: Ang, Y. S. , Gaspar-Maia, A. , Lemischka, I. R. and Bernstein,E.

Initially, when scientists were beginning to grasp the concept of DNA and its storage genes, they believed certain genes present in the DNA sequence would be expressed and those who were not originally expressed would remain hidden throughout that organisms’ …

The process of apoptosis is a cascade involving several reactions and processes that are controlled by enzymes. In these processes destruction of proteins and other contents of the cell are brought about. There are mainly two apoptotic pathways namely the …

Genes are found in every cell of your body, controlling how each cell functions. Mutations in genes, either inherited from your mother and father or from damage that occurred during a person’s life, contribute to the growth and development of …

Breast cancer remains a significant scientific, clinical and societal challenge. This gap analysis has reviewed and critically assessed enduring issues and new challenges emerging from recent research, and proposes strategies for translating solutions into practice. Methods. More than 100 internationally …

David from Healtheappointments:

Hi there, would you like to get such a paper? How about receiving a customized one? Check it out https://goo.gl/chNgQy